[Karen W.]

Thanks Iko... Love the fireworks!

[iko (OP)]

Talking about strangest presentations!

Orbital manifestation of whipple's disease: An atypical case.

Lieger O, Otto S, Clemetson IA, Arnold M, Iizuka T.
Department of Cranio-Maxillofacial Surgery, University of Bern, Switzerland (Director and Head: Professor Tateyuki Iizuka, MD, DDS, PhD, FEBOMFS).

BACKGROUND: Whipple's disease is a systemic disorder caused by an infection with a gram-positive bacillus, Tropheryma whipplei. Almost every organ system can be affected in Whipple's disease, resulting in varying clinical symptoms.
CASE REPORT: As far as we are aware, this report of a 61-year-old male is the first presenting with a periorbital manifestation of the disease, with severe exophthalmos and optic nerve involvement, leading to rapid visual loss.
This emergency case was successfully treated by a surgical orbital decompression combined with systemic use of antibiotics and steroids.
CONCLUSION: Whipple's disease can affect the periorbital tissues and the optic nerve, causing massive exophthalmos and serious transient visual loss. In such a case surgical decompression of the affected orbit combined with antibiotics and steroids is a recommended valid treatment option.

J Craniomaxillofac Surg. 2007 Oct 26;

http://itp.nyu.edu/projects_documents/1145268301_E_bye_E.jpg

[Karen W.]

 Does Whipples ever effect vision by making you have Blurred vision..? Kind of garbled up for short periods of time. I am talking like 4 or 5 minutes then poof gone back to normal!

[iko (OP)]

Yes Karen,

like several other more common infectious agents,
even Whipple bacteria may cause optic neuritis,
i.e. inflammation of the eye nerve, our TV cable...
Nevertheless, scattered episodes of blurred vision are quite
common and in many cases totally benign, certainly not a
specific symptom of an hidden infectious disease.

Here is a report of blurred vision in neuroborreliosis:

Motion-onset and pattern-reversal visual evoked potentials in diagnostics of neuroborreliosis.

Kubová Z, Szanyi J, Langrová J, Kremlácek J, Kuba M, Honegr K.
Department of Pathophysiology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic. kubova@lfhk.cuni.cz

Neuroborreliosis is a form of borreliosis that affects the central and/or peripheral nervous system. Although it can mimic neurologic and ophthalmologic disorders such as multiple sclerosis and optic neuritis, visual evoked potential (VEP) examination is usually not used in neuroborreliosis diagnostics. Combined VEP testing (pattern-reversal VEPs and VEPs produced in response to linear and radial motion) was performed in 81 patients with neuroborreliosis verified by laboratory results (positive polymerase chain reaction or intrathecal antibodies production). Thirty-four patients reported diplopia or blurred vision related to borreliosis. In 33 (40%) patients the VEPs were delayed: motion-onset VEPs were pathologic in 22 (27%) patients, reversal VEPs in 5 (6%) patients, and both VEP types in 6 (7%) patients. The findings suggest that VEP testing (especially the motion-onset VEP testing) can confirm CNS involvement. Much higher sensitivity of motion-onset VEPs in comparison with reversal VEPs can result from rather selective (earlier) involvement of the magnocellular system or the dorsal stream of the visual pathway.

J Clin Neurophysiol. 2006 Oct;23(5):416-20.

Nonpathologic Causes of Blurred Vision

Refractive Errors

Functional Loss of Vision

Pathologic Causes of Blurred Vision

Sudden, Unilateral, Painless Loss of Vision

Sudden, Unilateral, Painful Loss of Vision

Sudden, Bilateral, Painless Loss of Vision

Sudden, Bilateral, Painful Loss of Vision

Gradual, Unilateral, Painless Loss of Vision

Gradual, Unilateral, Painful Loss of Vision

Gradual, Bilateral, Painless Loss of Vision

Gradual, Bilateral, Painful Loss of Vision

Conclusions

Source Information

From Ophthalmic Consultants of Boston, Boston.

Address reprint requests to Dr. Shingleton at 50 Staniford St., Suite 600, Boston, MA 02114, or at bjshingleton@eyeboston.com

source: NEJMed.  http://content.nejm.org/cgi/content/short/343/8/556

[iko (OP)]

When typical symptoms of Whipple disease
like diarrhea, malabsorption, anemia are
missing...to diagnose it is very hard:

Whipple's disease with muscle impairment.

Puget M, Iwaz J, Tristan A, Streichenberger N.Department of Internal Medicine, Centre Hospitalier Lyon-Sud, 165 Chemin du Grand Revoyet, 69495 Pierre-Bénite, France. mpuget@ch-valence.fr

A 67-year-old man presented with myalgia, muscle atrophy, and a history of seronegative polyarthritis. Blood tests showed inflammation but no hematologic or immunologic abnormalities. Muscle biopsy revealed no vasculitis or myositis but Tropheryma whipplei was detected by polymerase chain reaction in muscle, blood, and duodenum specimens; this was confirmed by immunohistochemistry. Ceftriaxone led to clinical improvement. Although rare, Whipple's disease should be considered in the differential diagnosis of diffuse myopathy.

Muscle Nerve. 2006 Dec;34(6):794-8.

http://www.terragalleria.com/images/italy/ital7126.jpeg

[iko (OP)]

Autoptic cases.
At the end of this topic,
to never forget that a consistent
number of whipple-diagnoses are still...
...autoptic. Unfortunately.

Whipple Disease: A Case Report and Review of the Literature

MAJ Jeannie Muir-Padilla, COL Jerome B. Myers.
Department of Pathology, Madigan Army Medical Center, Tacoma, Wash.
Archives of Pathology and Laboratory Medicine: 2005:129, No. 7, pp. 933–936.

...
A 62-year-old woman presented to her primary care physician complaining of worsening shortness of breath. The patient's past medical history included restrictive cardiomyopathy of unknown etiology, sick sinus syndrome with pacemaker placement, congestive heart failure, arthritis, hepatomegaly, spontaneous bacterial peritonitis, intermittent diarrhea, and hypothyroidism.

Physical examination revealed a febrile woman with mild venous jugular distension, bilateral diffuse crackles in the lower and mid lung fields, and a distended abdomen with guarding and a positive fluid wave.

Examination of the peritoneal fluid revealed 4+ neutrophils with no bacteria. The patient was treated with furosemide for her diagnosis of congestive heart failure and appropriate antibiotic therapy for spontaneous bacterial peritonitis. She was discharged on hospital day 8 after showing improvement in her oxygenation status. Four days after discharge from the hospital, the patient again complained of difficulty breathing. Emergency medical personnel were summoned, and the patient was found apneic and pulseless with perioral cyanosis. Based on the previously documented wishes of the patient, resuscitative measures were not undertaken, and the patient was pronounced dead.
...

free full-text available on line:

http://arpa.allenpress.com/arpaonline/?request=get-document&doi=10.1043%2F1543-2165(2005)129%5B933:WDACRA%5D2.0.CO%3B2

[Karen W.]

Wow Iko...I am being treated with the same medication.Furosemide 40 mg tabs, seems to be common treatment They also have me on the Trimeterine/HCTZ 37.5/25 caps.. Blood Pressure and diuretic.

[quote/] (Iko)A 62-year-old woman presented to her primary care physician complaining of worsening shortness of breath. The patient's past medical history included restrictive cardiomyopathy of unknown etiology, sick sinus syndrome with pacemaker placement, congestive heart failure, arthritis, hepatomegaly, spontaneous bacterial peritonitis, intermittent diarrhea, and hypothyroidism.[quote}

These all sound way too familiar...

[iko (OP)]

Wow Iko...I am being treated with the same medication.Furosemide 40 mg tabs, seems to be common treatment They also have me on the Trimeterine/HCTZ 37.5/25 caps.. Blood Pressure and diuretic.

(Iko)A 62-year-old woman presented to her primary care physician complaining of worsening shortness of breath. The patient's past medical history included restrictive cardiomyopathy of unknown etiology, sick sinus syndrome with pacemaker placement, congestive heart failure, arthritis, hepatomegaly, spontaneous bacterial peritonitis, intermittent diarrhea, and hypothyroidism.

These all sound way too familiar...

Hi Karen,

please don't improvise: too many diseases give that picture!
This is actually an example of atypical presentation...
BTW are you taking any antibiotic?

ikod

[Karen W.]

[size=07pt]
(sorry Iko.. I accidently put my post in yours, all fixed..)[/size]

No worries I won't I don't want to even guess at anything.. I want them just to figure out what it is that is really wrong and stop just treating symptoms..It is really frustrating...

I tried to go for my appointment this last week and they delayed it due to care provider problems.. they were having some staff turnover and rescheduled me for the 29th unless she can slip me into an earlier spot then we will start. So far no antibiotics for the infection... I must say.. Have been feeling crudy and having a hard time taking full breaths.. The coughing has become much worse with lots of clear fluid when it allows it to come up.. some times the cough is just unproductive and dry. Chest hurts when I try to breathe in a normal breath. Yesterday was coughing so Hard My head felt like something popped a couple inches down into the center. That has happened a couple times.. OOOOH sorry I am rambling ... no antibiotics as of yet!

[iko (OP)]

February 2008 Whipple update:
less invasive diagnostic tools are coming!

Advances in Tropheryma whipplei research:
the rush to find biomarkers for Whipple's disease.

 
Kowalczewska M, Raoult D.
Unité des Rickettsies, CNRS UMR 6020, IFR 48, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille, France. kmalgo@yahoo.fr

Whipple's disease (WD) is a systemic chronic infection, caused by the Gram-positive bacterium Tropheryma whipplei. There are several clinical traits linked to WD: histological lesions in the GI tract in association with diverse clinical manifestations (classic WD), endocarditis with negative blood cultures, and isolated neurological infection. WD is rare, predominantly affects middle-aged men and is fatal without treatment. The most recent strategy for diagnosing WD uses the results of diastase-resistant periodic acid Schiff staining and PCR in parallel, both performed on involved organ/tissue biopsy (small intestine, cardiac valve and cerebrospinal fluid). The generation of rabbit polyclonal antibodies has enabled the detection of the bacterium in tissues by immunohistochemical staining. However, the diagnosis of WD remains an invasive procedure. The recent achievement of stable bacterial culture and sequencing of the T. whipplei genome has opened a framework for the development of a biomarker platform. Several studies in different fields have been performed, for example, transcriptomics, immunoproteomics and comparative proteomics. Biomarker candidates have been proposed for the development of less invasive procedures for diagnosing WD.

Future Microbiol. 2007 Dec;2:631-42.

[understudy]

newbielink:http://www.ncbi.nlm.nih.gov/pubmed/18287323 [nonactive]

"We report a case of prosthetic hip infection due to Tropheryma whipplei in a 74-year-old man not previously known to have Whipple's disease. Diagnosis was based on systematic 16S rRNA gene amplification and sequencing of samples obtained during revision hip arthroplasty."

[iko (OP)]

Scattered reports allow including WD between
the infectious causes of hip arthritis:

"Hipple Disease"   []

Whipple's disease diagnosed at hip arthroplasty.

Farr M, Hollywell CA, Morris CJ, Struthers GR, Bacon PA, Walton KW.
A patient is reported with a six-year history of seronegative inflammatory arthritis, lymphadenopathy, and a rash. Many investigations, including repeat jejunal and synovial needle biopsies, failed to establish the diagnosis. Eventually right hip destruction led to arthroplasty. Synovial membrane obtained at operation was examined by electron microscopy and organisms were found with the morphological characteristics of those in patients where the diagnosis was firmly established as Whipple's disease. We propose that Whipple's disease should be seriously considered as a rare but distinct and treatable possibility in the differential diagnosis of seronegative inflammatory arthritis.

Ann Rheum Dis. 1984 Jun;43(3):526-9.

[iko (OP)]

Recent news from the official Whipple-beasts hunting experts:

Prevalence of asymptomatic Tropheryma whipplei carriage among humans and nonhuman primates.

Fenollar F, Trani M, Davoust B, Salle B, Birg ML, Rolain JM, Raoult D.
Université de la Méditerranée, Unité des Rickettsies, CNRS UMR 6020, Faculté de Médecine, Marseille cedex, France.

BACKGROUND: The reservoir of the agent of Whipple disease is unknown. Asymptomatic carriage of Tropheryma whipplei in human stool and saliva is controversial. METHODS: Stools and saliva specimens from 231 workers at a sewage treatment facility and from 10 patients with Whipple disease, stool specimens from 102 healthy people, and stool specimens from 127 monkeys or apes were tested for T. whipplei DNA by a quantitative real-time polymerase chain reaction with probe detection. Genotyping and culture of T. whipplei-positive samples were performed. RESULTS: Asymptomatic carriage in stool was found in humans (ranging from a prevalence of 4% in the control group to 12% among a subgroup of sewer workers) but not in monkeys and apes. The T. whipplei load in stool was significantly lower in carriers than in patients with Whipple disease (P < .001). There was a significant prevalence gradient associated with employment responsibilities at the sewage treatment facility: workers who cleaned the underground portion of the sewers were more likely than other workers to carry T. whipplei in stool. Seven of 9 sewer workers tested positive 8 months later. Patients with Whipple disease were significantly more likely to have T. whipplei-positive saliva specimens (P = .005) and had a significantly greater T. whipplei load in saliva (P = .015), compared with asymptomatic stool carriers from the sewage facility. All non-stool carriers had T. whipplei-negative saliva specimens. T. whipplei strains were heterogeneic among sewer workers but identical within individual workers.
CONCLUSION: Chronic asymptomatic carriage of T. whipplei occurs in humans. Bacterial loads are lower in asymptomatic carriers, and the prevalence of carriage increases with exposure to sewage.

J Infect Dis. 2008 Mar 15;197(6):880-7.

http://www.genomenewsnetwork.org/articles/03_03/whipple_art.shtml

[Karen W.]

Something so beautiful can be so nasty... what a shame!

[iko (OP)]

June 2008 update:
most intriguing cases from...Italy!
Mammamia!

Whipple Disease: Unusual Presentation of a Protean and Sometimes Confusing Disease.

Lo Monaco A, Govoni M, Zelante A, Rinaldi R, Scorrano AR, Di Stefano M, Trotta F.Dipartimento di Medicina Clinica e Sperimentale, Sezione di Reumatologia-Università di Ferrara, Ferrara, Italy.

OBJECTIVES: To describe an unusual case of Whipple disease (WD) with confusing clinical features at onset and to discuss the diagnostic challenges for the clinician. METHODS: Description of a new case of this rare disease and thorough discussion of the atypical clinical manifestations at onset. A literature review, concerning the unusual onset, by means of a MEDLINE search from 1966 to 2007 was done.
RESULTS: A 39-year-old man with sudden bilateral blurred vision due to retinal vasculitis and concomitant rapidly evolving symmetrical neurosensory bilateral hearing loss as initial features of WD is described. Due to the clinical manifestations resembling systemic vasculitis, high-dose corticosteroid and pulse cyclophosphamide therapy were started with subsequent appearance of gastrointestinal symptoms (diarrhea and weight loss) and spiking fever, suggesting superimposed infection. After a complete evaluation, including gastroscopy, extensive duodenal-jejunal mucosal involvement was seen, while diffuse infiltration of the duodenal lamina propria with periodic acid-Schiff-positive foamy macrophages was observed on the histological sample. The diagnosis was confirmed by reverse transcriptase-polymerase chain reaction for the DNA of Tropheryma whippelii. To our knowledge, no previous similar clinical onset of WD has been described.
CONCLUSIONS: To avoid misdiagnosis and therapeutic mistakes, clinicians should be aware of unusual presentations of WD. Because this etiological agent is a difficult to isolate bacterium, diagnosis may be especially problematic in cases without intestinal involvement at onset.

Semin Arthritis Rheum. 2008 Jun 5. [Epub ahead of print]

http://www.ferrara.biz/ferrara.jpg

[Karen W.]

Hey Iko.. I have been reading and reading this entire thread again, and throughout the thread there is reference to: polymerase chain reaction. I was wondering if you could take few minutes and explain this procedure to me, and exactly what it is and how they run the test or how it works...?

Also in the last post I see the 1rst reference to: reverse transcriptase-polymerase chain reaction for the DNA of Tropheryma whippelii...

If it had been used in previous posts I missed it. I am curious about both..?

[iko (OP)]

Hi Karen,

Polymerase chain reaction allows you to find DNA or RNA from viruses or bacteria that hide somewhere in our body.
It is highly sensitive (few 'copies' of DNA/mL spotted easily) and very specific: special 'primers' used to start the reaction stick only to a particular sequence of DNAbases...

http://highered.mcgraw-hill.com/olc/dl/120078/micro15.swf

The big thing is that -to confirm an infectious disease- we don't rely anymore only on antibody production by the host, antibodies that might be absent or a memory of a previous infection: we look for bits and pieces of the very germs that came on board.  Even searching for bugs in biopsies by microscope is difficult and messy(aggressive) enough...particularly in the case of intracellular germs like T.whipplei.

BTW, you may consider reverse-transcriptase part of the PCR test itself...same thing to spot and amplify little bits of nucleic acids, million copies that become 'visible' in the end, allowing a diagnosis of infection.

[Karen W.]

Thank you IKO and thanks for the link.. I read your post and will now take a look at that link...
Thanks again..

[Karen W.]

nice illustration IKO! Thanks for the link...

[tanya222]

Where can I get a PCR test for WD?

I am in Ontario Canada. 

Also does it work on regular blood test, or does it have to come from the intestine?

Great thread IKO, I don't know how you keep finding these case reports, I can't find them anywhere but here!